The fetus secretes insulin appropriately in response to a number of stimuli, particularly alteration of circulating glucose levels. A possible role for prostaglandins in the inhibition of glucose-induced early phase insulin secretion has recently been demonstrated in the adult diabetic. Since glucose-induced early phase insulin release is minimal in the fetal lamb, prostaglandin synthesis inhibitors were injected to observe possible effects upon the stimulation of glucose induced early phase insulin release. No acute effects, however, were noted. In addition, a potential model for the fetus of the pregnant diabetic is being developed by infusing glucose into one of twin lambs for periods up to 17 days (mean 8 days). Chronic hyperglycemia and hyperinsulinism result in this model. Progressive increases in fetal glucose infusion and glucose level are associated with a decline in fetal arterial O2 content. If severe, metabolic acidosis develops when the lambs are severely hypoxemic and in utero demise ultimately follows. No effects upon growth parameters or insulin release have been noted in these relatively short infusion periods. A role for glucagon in fetal metabolism has yet to be delineated. Both pharmacologic and physiologic hyperglucagonemia in the fetal lamb causes an acute elevation in fetal plasma glucose. A concomitant fall in the fetal glucose V-A difference, glucose/O2 quotient and net fetal glucose consumption all suggest an acute fetal glycogenolytic response. Fetal ketone production post-glucagon, unlike the adult situation, is unaltered. Glucagon injection did cause significant fetal insulin release. This release was related to the dose of glucagon utilized but not to the hyperglycemia produced. Chronic glycagon infusions to assess changes in fetal gluconeogenic capacity are planned.